Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Category:

Vasodilator—

IndicationsUnaccepted
Although papaverine has previously been classed as a “grandfather drug” and exempted from FDA's DESI classification, the Peripheral and Central Nervous System Drugs Advisory Committee of the FDA has concluded after studies and hearings that, in spite of its proven vasodilating effects, the medication has not been shown to be effective for its claimed indications. These include use as a smooth muscle relaxant in the treatment of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias; and for visceral spasm as in ureteral colic, biliary colic, or gastrointestinal colic.

Papaverine has a direct, nonspecific relaxant effect on vascular, cardiac, and other smooth muscle. {02}Absorption:

Variable; oral bioavailability is usually about 54%, but absorption from extended-release dosage forms is poor.Protein binding:

Very high (approximately 90%).Biotransformation:

Hepatic.Half-life:

0.5 to 2 hours (variable; may be as long as 24 hours).Elimination:
Renal (as metabolites).
In dialysis—Removable by hemodialysis.

Precautions to ConsiderPregnancy/Reproduction

Pregnancy—
Studies have not been done in humans.

Studies have not been done in animals.

FDA Pregnancy Category C.Breast-feeding

It is not known whether papaverine is distributed into breast milk. However, problems in humans have not been documented.Pediatrics

Appropriate studies on the relationship of age to the effects of papaverine have not been performed in the pediatric population. However, pediatrics-specific problems that would limit the usefulness of this medication in children are not expected.

Geriatrics

Appropriate studies on the relationship of age to the effects of papaverine have not been performed in the geriatric population. However, the risk of papaverine-induced hypothermia may be increased in elderly patients.Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Levodopa (concurrent use may decrease the therapeutic effects of levodopa because of possible blockade of dopamine receptors by papaverine)

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Except under special circumstances, this medication should not be used intravenously when the following medical problem exists:» Atrioventricular (AV) heart block, complete (large doses can depress AV and intraventricular conduction and produce serious arrhythmias)

Risk-benefit should be considered when the following medical problems exist
Angina or
Myocardial infarction, recent or
Stroke, recent (ischemia may be exacerbated by a possible “steal effect” since papaverine has a greater effect on peripheral than cerebral and coronary vessels, leading to a further decrease in flow to ischemic areas)

Sensitivity to papaverine{02}Patient monitoringThe following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:Those indicating need for medical attentionIncidence rareHepatic hypersensitivity (yellow eyes or skin)

With parenteral administrationThrombosis (redness, swelling, or pain at injection site)

Those indicating need for medical attention only if they continue or are bothersomeWith rapid parenteral administrationDeep breathingfast heartbeatflushing of facehypotension (dizziness)

Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:Blurred or double visiondrowsinessweakness

Treatment of overdose
Treatment of acute poisoning consists of: Removal or delay of absorption of papaverine by administration of tap water, milk, or activated charcoal, and removal of stomach contents by gastric lavage or emesis, followed by catharsis; appropriate measures for treatment of coma or respiratory depression and maintenance of blood pressure; hemodialysis may be useful.

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Papaverine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):Before using this medication» Conditions affecting use, especially:Sensitivity to papaverine

Use in the elderly—Increased risk of hypothermiaOther medical problems, especially complete atrioventricular heart block (for intravenous administration only) and myocardial depressionProper use of this medication
Taking with or following meals, milk, or antacids, to reduce nausea

Proper administration of extended-release capsules: Swallowing whole without crushing, breaking, or chewing before swallowing or, if too large to swallow, mixing contents with jam or jelly and swallowing without chewing

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storagePrecautions while using this medication
Checking with physician before discontinuing medication

Avoiding smoking because nicotine constricts blood vessels

» Caution when getting up from a lying or sitting position or when climbing stairs

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.